NCT01244490

Efficacy and Safety of Extended-release Guanfacine Hydrochloride in Children and Adolescents Aged 6-17 Years With Attention-Deficit/Hyperactivity Disorder (ADHD)

Completed Phase 3 Results posted Last updated 2 July 2021

What this trial tests

Phase 3 trial testing Extended-release Guanfacine Hydrochloride in Attention Deficit Hyperactivity Disorder in 338 participants. Completed in 1 May 2013.

Timeline

17 January 2011

Primary endpoint
1 May 2013

1 May 2013

Quick facts

Lead sponsor	Shire
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	338
Start date	17 January 2011
Primary completion	1 May 2013
Estimated completion	1 May 2013
Sites	66 locations across France, Italy, Ukraine, Austria, Sweden, Ireland, United Kingdom, Germany

Drugs / interventions tested

• Extended-release Guanfacine Hydrochloride
• Atomoxetine Hydrochloride — full drug profile →
• Placebo Comparator

Conditions studied

• Attention Deficit Hyperactivity Disorder — all drugs for Attention Deficit Hyperactivity Disorder →

Sponsor

Shire — full company profile →

Who can join

Adults 6 to 17, any sex, with Attention Deficit Hyperactivity Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 10/13 - Last Observation Carried Forward (LOCF) Primary · Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Group	Value	95% CI
Placebo	-15.0	± 1.1612
Guanfacine Hydrochloride	-23.9	± 1.1531
Atomoxetine Hydrochloride	-18.8	± 1.1549

Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores Secondary · Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Group	Value	95% CI
Placebo	44.1
Guanfacine Hydrochloride	67.9
Atomoxetine Hydrochloride	56.3

Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Learning and School Domain Scores at Week 10/13 - LOCF Secondary · Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

The WFIRS-P Learning in School Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Group	Value	95% CI
Placebo	-0.419	± 0.0537
Guanfacine Hydrochloride	-0.636	± 0.0527
Atomoxetine Hydrochloride	-0.581	± 0.0534

Change From Baseline in the WFIRS-P Family Domain Score at Week 10/13 - LOCF Secondary · Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

The WFIRS-P Family Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Group	Value	95% CI
Placebo	-0.409	± 0.0568
Guanfacine Hydrochloride	-0.617	± 0.0558
Atomoxetine Hydrochloride	-0.499	± 0.0566

Clinical Global Impression-Severity of Illness (CGI-S) - LOCF Secondary · Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill). Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

1 (Normal, not at all ill)

Group	Value	95% CI
Placebo	9.9
Guanfacine Hydrochloride	14.3
Atomoxetine Hydrochloride	6.3

2 (Borderline mentally ill)

Group	Value	95% CI
Placebo	15.3
Guanfacine Hydrochloride	23.2
Atomoxetine Hydrochloride	19.6

3 (Mildly ill)

Group	Value	95% CI
Placebo	20.7
Guanfacine Hydrochloride	31.3
Atomoxetine Hydrochloride	32.1

4 (Moderately ill)

Group	Value	95% CI
Placebo	20.7
Guanfacine Hydrochloride	22.3
Atomoxetine Hydrochloride	19.6

5 (Markedly ill)

Group	Value	95% CI
Placebo	25.2
Guanfacine Hydrochloride	5.4
Atomoxetine Hydrochloride	13.4

6 (Severely ill)

Group	Value	95% CI
Placebo	6.3
Guanfacine Hydrochloride	3.6
Atomoxetine Hydrochloride	7.1

7 (Amongst the most extremely ill)

Group	Value	95% CI
Placebo	1.8
Guanfacine Hydrochloride	0
Atomoxetine Hydrochloride	1.8

Health Utilities Index-2/3 (HUI 2/3) Scores - LOCF Secondary · Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Group	Value	95% CI
Placebo	0.927	± 0.0950
Guanfacine Hydrochloride	0.922	± 0.0908
Atomoxetine Hydrochloride	0.913	± 0.1052

Change From Baseline in the WFIRS-P Global Score at Week 10/13 - LOCF Secondary · Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

The WFIRS-P Global Score is the mean of 50 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Group	Value	95% CI
Placebo	-0.321	± 0.0387
Guanfacine Hydrochloride	-0.487	± 0.0374
Atomoxetine Hydrochloride	-0.425	± 0.0384

Change From Baseline in the WFIRS-P Academic Performance Domain Score at Week 10/13 - LOCF Secondary · Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

The WFIRS-P Academic Performance Domain is the mean of 4 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Group	Value	95% CI
Placebo	-0.555	± 0.0784
Guanfacine Hydrochloride	-0.766	± 0.0757
Atomoxetine Hydrochloride	-0.681	± 0.0759

Change From Baseline in the WFIRS-P Behavior in School Domain Score at Week 10/13 - LOCF Secondary · Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

The WFIRS-P Behavior in School Domain is the mean of 6 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Group	Value	95% CI
Placebo	-0.363	± 0.0512
Guanfacine Hydrochloride	-0.592	± 0.0502
Atomoxetine Hydrochloride	-0.544	± 0.0509

Change From Baseline in the WFIRS-P Life Skills Domain Score at Week 10/13 - LOCF Secondary · Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

The WFIRS-P Life Skills Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Group	Value	95% CI
Placebo	-0.383	± 0.0422
Guanfacine Hydrochloride	-0.477	± 0.0411
Atomoxetine Hydrochloride	-0.450	± 0.0422

Change From Baseline in the WFIRS-P Child Self-Concept Domain Score at Week 10/13 - LOCF Secondary · Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

The WFIRS-P Child Self-Concept Domain is the mean of 3 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Group	Value	95% CI
Placebo	-0.312	± 0.0544
Guanfacine Hydrochloride	-0.361	± 0.0528
Atomoxetine Hydrochloride	-0.390	± 0.0536

Change From Baseline in the WFIRS-P Social Domain Score at Week 10/13 - LOCF Secondary · Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

The WFIRS-P Social Domain is the mean of 7 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Group	Value	95% CI
Placebo	-0.322	± 0.0537
Guanfacine Hydrochloride	-0.555	± 0.0519
Atomoxetine Hydrochloride	-0.434	± 0.0532

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 1/111 (1%)

Deaths: —

Guanfacine Hydrochloride

Serious: 1/114 (1%)

Deaths: —

Atomoxetine Hydrochloride

Serious: 0/112 (0%)

Deaths: —

Serious adverse events (1 terms)

Reaction	System	Placebo	Guanfacine Hydrochloride	Atomoxetine Hydrochloride
Syncope	Nervous system disorders	—	—	—

Other adverse events (16 terms — click to expand)

Reaction	System	Placebo	Guanfacine Hydrochloride	Atomoxetine Hydrochloride
Somnolence	Nervous system disorders	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Fatigue	General disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Increased appetite	Metabolism and nutrition disorders	—	—	—
Anxiety	Psychiatric disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
Pyrexia	General disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Nervousness	Psychiatric disorders	—	—	—

Most-reported serious reactions: Syncope.

Data from ClinicalTrials.gov NCT01244490 adverse events section.

Sponsor's own description

For children and adolescents, how does SPD503 compare to placebo for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD).

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Correlations Between Clinical Trial Outcomes Based on Symptoms, Functional Impairments, and Quality of Life in Children and Adolescents With ADHD.
   Coghill DR, Joseph A, Sikirica V, Kosinski M, et al · · 2019 · cited 17× · PMID 28836895 · DOI 10.1177/1087054717723984
2. Methods to Develop an <i>in silico</i> Clinical Trial: Computational Head-to-Head Comparison of Lisdexamfetamine and Methylphenidate.
   Gutiérrez-Casares JR, Quintero J, Jorba G, Junet V, et al · · 2021 · cited 13× · PMID 34803764 · DOI 10.3389/fpsyt.2021.741170
3. Efficacy and Tolerability of Different Interventions in Children and Adolescents with Attention Deficit Hyperactivity Disorder.
   Luan R, Mu Z, Yue F, He S. · · 2017 · cited 8× · PMID 29180967 · DOI 10.3389/fpsyt.2017.00229
4. Functional impairment outcomes in clinical trials of different ADHD medications: post hoc responder analyses and baseline subgroup analyses.
   Coghill DR, Werner-Kiechle T, Farahbakhshian S, Bliss C, et al · · 2021 · cited 7× · PMID 32691164 · DOI 10.1007/s00787-020-01586-5
5. Guanfacine extended release for children and adolescents with attention-deficit/hyperactivity disorder: efficacy following prior methylphenidate treatment.
   Huss M, Sikirica V, Hervas A, Newcorn JH, et al · · 2016 · cited 7× · PMID 27226715 · DOI 10.2147/ndt.s94158
6. A simple formula for enumerating comparisons in trials and network meta-analysis.
   Shokraneh F, Adams CE. · · 2019 · cited 2× · PMID 30863537 · DOI 10.12688/f1000research.17352.2